ICAM-1 (Lys469Glu) and PECAM-1 (Leu125Val) polymorphisms in diffuse astrocytomas

Cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) play an important role in glioma invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and PECAM-1 could be associated with glioma development and progression. Single-nucleotide polymorphism in codon 469 of ICAM-1 and codon 125 of PECAM-1 were examined in 158 patients with astrocytomas and 162 controls using polymerase chain reaction and restriction enzyme analysis. The distribution of PECAM-1 polymorphic genotypes in astrocytomas did not show any significant difference. However, a specific ICAM-1 genotype (G/G, corresponding to Lys469Glu) exhibited higher frequency in grade II astrocytomas compared to controls, grade III, and grade IV astrocytomas; suggesting that this polymorphism could be involved in the development of grade II astrocytomas.     

Should endometrial polyps be removed in patients with postmenopausal bleeding?—an assessment of study designs and report of a failed randomised controlled trial (ISRCTN73825127)

We describe the design of a randomised controlled trial to evaluate the efficacy of endometrial polyp removal in women with postmenopausal bleeding. We designed a trial in which patients with postmenopausal bleeding and endometrial thickness >4 mm undergo hysteroscopy. If during hysteroscopy an endometrial polyp was diagnosed, patients were asked to participate in this trial and after informed consent allocated to immediate removal of the polyp or expectant management. This trial suffered from lack of recruitment related both to doctors seeking for informed consent as well as to patients' unwillingness to participate in this trial. However, a randomised controlled trial on this subject is still necessary to evaluate the efficacy of uterine cavity evaluation in the diagnostic work-up of women with postmenopausal bleeding, focussing on benign pathology. Therefore, we propose an alternative design, which might be more feasible.     

AS-1 red cells for neonatal transfusions: a randomized trial assessing donor exposure and safety

BACKGROUND: Despite recent optimism about the use of erythropoietin therapy to treat the anemia of prematurity, very-low-birth-weight infants who are severely ill receive multiple red cell (RBC) transfusions. Many physicians transfuse relatively fresh RBCs to newborn infants, exposing them to multiple donors and possibly increasing their risk of acquiring transfusion-transmitted infections. STUDY DESIGN AND METHODS: A randomized, single-blind clinical trial was conducted to determine, as the primary endpoint, whether RBCs collected from one dedicated donor and stored for < or = 42 days in AS-1 storage media could safely supply all small-volume RBC transfusions (15 mL/kg/dose) needed by very-low-birth-weight infants (0.6-1.3 kg) during the first 84 days of life. Secondary endpoints were the assessment of the possible adverse clinical and biochemical effects of transfusing AS- 1 RBCs stored for < or = 42 days. Control infants received identical nursery care, except they received fresh RBCs stored < or = 7 days in CPDA-1. RESULTS: Infants transfused with AS-1 RBCs were exposed to a mean of 1.6 donors,-compared with an exposure to 3.7 donors for infants given CPDA-1 RBCs (p < 0.05). Neither clinical transfusion reactions nor the results of multiple laboratory tests were significantly different in infants who received slow transfusions (15 mL/kg) of AS-1 RBCs stored for < or = 42 days and in infants who received the same volume of CPDA-1 RBCs stored < or = 7 days. CONCLUSION: AS-1 RBCs, usually from only one dedicated donor, can safely supply all RBCs needed by most very-low-birth-weight infants-a practice that decreases donor exposure and likely increases transfusion safety.     

差示分光光度法测定制剂中硝苯啶的含量

利用硝苯啶溶液对光不稳定的性质,在波长350nm处测其光照前后的吸收度差值(△A),△A与硝苯啶乙醇溶液浓度在10～60μg/ml范围内呈线性关系。使用本法对硝苯啶片进行了含量测定,并对其类似物进行了干扰试验,排除了组分的干扰。该法的精密度日内为1.3％,日间为1.9％,平均回收率为99.96％。方法简便、快速,不需色谱等分离手段即可达到分析目的,专一性、重复性均较好,是分析硝苯啶制剂的一种新途径。     

芳香稠环取代酰氯的合成

芳香稠环取代酰氯的合成胡文祥恽榴红张连锋（国防科工委军事医药研究发展中心，北京１００１０１；军事医学科学院毒物药物研究所，北京１００８５０）许多高效药物和激素用量甚少，分布全身代谢后血药浓度更低，并且它们又往往不含强烈的发色基团，因此在药代...     

Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal

Smoking is the largest preventable cause of death in the United States. Furthermore, a recent study found that <10% of quit attempts resulted in continuous abstinence for 1 year. With the introduction of pharmacotherapies like Chantix (varenicline), a selective α4β2 nicotinic partial agonist, successful quit attempts have significantly increased. Therefore, novel subtype-specific nicotinic drugs, such as sazetidine-A, present a rich area for investigation of therapeutic potential in smoking cessation. The present studies examine the anxiety-related behavioral and functional effects of the nicotinic partial agonists varenicline and sazetidine-A during withdrawal from chronic nicotine in mice. Our studies indicate that ventral hippocampal-specific infusions of sazetidine-A, but not varenicline, are efficacious in reducing nicotine withdrawal-related anxiety-like phenotypes in the novelty-induced hypophagia (NIH) paradigm. To further investigate functional differences between these partial agonists, we utilized voltage-sensitive dye imaging (VSDi) in ventral hippocampal slices to determine the effects of sazetidine-A and varenicline in animals chronically treated with saline, nicotine, or undergoing 24 h withdrawal. These studies demonstrate a functional dissociation of varenicline and sazetidine-A on hippocampal network activity, which is directly related to previous drug exposure. Furthermore, the effects of the nicotinic partial agonists in VSDi assays are significantly correlated with their behavioral effects in the NIH test. These findings highlight the importance of drug history in understanding the mechanisms through which nicotinic compounds may be aiding smoking cessation in individuals experiencing withdrawal-associated anxiety.     

Tumorigenic potential of circulating prostate tumor cells

Circulating tumor cells (CTCs) have received intense scientific scrutiny because they travel in the bloodstream and are therefore well situated to mediate hematogenous metastasis. However, the potential of CTCs to actually form new tumors has not been tested. Popular methods of isolating CTCs are biased towards larger, more differentiated, non-viable cells, creating a barrier to testing their tumor forming potential. Without relying on cell size or the expression of differentiation markers, our objective was to isolate viable prostate CTCs from mice and humans and assay their ability to initiate new tumors. Therefore, blood was collected from transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and from human patients with metastatic castration-resistant prostate cancer (PCa). Gradient density centrifugation or red cell lysis was used to remove erythrocytes, and then leukocytes were depleted by magnetic separation using CD45 immunoaffinity beads. CTCs fractions from TRAMP mice and PCa patients were verified by immunocytochemical staining for cytokeratin 8 and EpCAM, and inoculated into immunodeficient mice. TRAMP tumor growth was monitored by palpation. Human tumor growth formation was monitored up to 8 months by ultrasensitive PSA assays performed on mouse serum. We found viable tumor cells present in the bloodstream that were successfully isolated from mice without relying on cell surface markers. Two out of nine immunodeficient mice inoculated with TRAMP CTCs developed massive liver metastases. CTCs were identified in blood from PCa patients but did not form tumors. In conclusion, viable CTCs can be isolated without relying on epithelial surface markers or size fractionation. TRAMP CTCs were tumorigenic, so CTCs isolated in this way contain viable tumor-initiating cells. Only two of nine hosts grew TRAMP tumors and none of the human CTCs formed tumors, which suggests that most CTCs have relatively low tumor-forming potential. Future studies should identify and target the highly tumorigenic cells.